There are three major ongoing projects in our laboratory: 1. Transcription factors that establish and maintain T-cell specific gene expression. TCF-1 imposes T cell identity early in T cell development, but the mechanisms employed are uncertain, and are the focus of intense investigation in our laboratory. We're using conditional alleles of TCF-1 to determine whether TCF-1 controls expression of a common set of T cell genes throughout development, or if TCF-1 instead plays different roles in mature T cells. 2. The development and function of innate lymphoid cells. Innate lymphoid cells have transcriptional programs that appear to mirror those of T cells. The comparison of innate lymphocyte cell development with T cell development provides an opportunity to understand the factors that underlie the shared as well as the unique features and functions of these apparently closely related cell lineages. We have identified the earliest known precursors committed to innate cell lineages, and are characterizing the functions of transcription factors expressed in these early innate lymphocyte precursors. 3. Transcription factors in thymic epithelial cells. Distinct transcription factors are expressed in fetal thymic epithelial cells, and in different subtypes of thymic epithelial cells. We are using knockout mice to determine the functions of these factors.